DETECTION OF THE C-MET PROTOONCOGENE PRODUCT IN NORMAL SKIN AND TUMORS OF MELANOCYTIC ORIGIN
DETECTION OF THE C-MET PROTOONCOGENE PRODUCT IN NORMAL SKIN AND TUMORS OF MELANOCYTIC ORIGIN
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DOI：
10.1002/path.1711740308
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发表时间：
1994-11-01
影响因子：
7.3
通讯作者：
PARSONS, PG
中科院分区：
文献类型：
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作者：
SAITOH, K;TAKAHASHI, H;PARSONS, PG
原癌基因c-met产物（c-MET）是一种受体酪氨酸激酶，作为肝细胞生长因子（HGF）的受体发挥作用。虽然c-MET的功能尚未完全阐明，但HGF刺激c-MET上酪氨酰残基的磷酸化并触发信号转导通路，导致与诸如碱性成纤维细胞生长因子和肥大细胞生长因子的协同因子促进黑素细胞的恶性进展。使用免疫组织化学方法，我们研究了c-MET在正常皮肤和各种黑素细胞肿瘤中的定位。在角质形成细胞、黑素细胞、皮脂腺细胞和皮肤的其他细胞中检测到c-MET。特别是，基底黑素细胞几乎总是显示核标记。黑素细胞痣通常主要表现为表皮细胞核染色，而只有少数情况下表现出明显的c-MET在真皮痣细胞的细胞质定位。c-MET在黑色素瘤细胞中的分布模式与良性病变基本相似，尽管检测的数量很少。培养的人黑色素瘤细胞也显示出主要的核标记，但对外源性c-MET配体HGF无反应。用葡萄糖苷酶抑制剂栗精胺治疗引起220 kD蛋白质的积累，而不减少正常处理的190 kD c-MET的量。虽然良性和恶性黑素细胞病变之间的c-MET分布没有显着差异，这表明黑素细胞的恶性转化可能与对HGF或其他生长调节因子的反应丧失有关。
The proto-oncogene c-met product (c-MET) is a receptor tyrosine kinase and functions as a receptor for hepatocyte growth factor (HGF). Although the function of c-MET has yet to be fully clarified, HGF stimulates the phosphorylation of tyrosyl residues on c-MET and triggers the signal transduction pathways, resulting in a contribution to the malignant progression of melanonocytes with synergic factors such as basic fibroblast growth factor and mast cell growth factor. Using immunohistochemical methods, we have studied the localization of c-MET in normal skin and various melanocytic tumours. c-MET was detected in keratinocytes, melanocytes, sebaceous cells, and other cells of the skin. In particular, basal melanocytes almost always showed nuclear labelling. Melanocytic naevi generally revealed predominantly nuclear staining of cells in the epidermis, whereas only a few cases showed a distinct cytoplasmic localization of c-MET in dermal naevus cells. The distribution pattern of c-MET in melanoma cells was basically similar to that of benign lesions, although the numbers tested were small. Cultured human melanoma cells also showed predominantly nuclear labelling, but were unresponsive to exogenous c-MET ligand HGF. Treatment with the glucosidase inhibitor castanospermine caused accumulation of protein at 220 kD, without diminishing the amount of normally-processed 190-kD c-MET. Although there was no significant difference in c-MET distribution between benign and malignant melanocytic lesions, it is suggested that malignant transformation of melanocytes may be associated with loss of response to HGF or other growth-regulating factors.